Related Experiment Video
Updated: Jun 4, 2025
A High-throughput Compatible Assay to Evaluate Drug Efficacy against Macrophage Passaged Mycobacterium tuberculosis
Published on: March 24, 2017
Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection
Alyssa Schami1,2, M Nurul Islam3,4, Matthew Wall5,6
1Population Health and Host Pathogen Interactions Programs, Texas Biomedical Research Institute, San Antonio, TX, USA. ASchami@txbiomed.org.
Abstract:
In recent decades, drug resistant (DR) strains of Mycobacterium tuberculosis (M.tb), the cause of tuberculosis (TB), have emerged that threaten public health. Although M.tb's complex and protective cell envelope has been widely studied, little is known about how levels of peripheral lipids change in relation to drug resistance. In this study, we examined levels of cell envelope lipids [phthiocerol dimycocerosates (PDIMs)], glycolipids [phosphatidyl-myo-inositol mannosides (PIMs)], and PIMs associated lipoglycans [lipomannan (LM); mannose-capped lipoarabinomannan (ManLAM)] of 22 M.tb strains that ranged in drug resistance profile. We show that the PDIMs:PIMs ratio increases as drug resistance increases, and provide evidence of PDIM isomers only present in the DR-M.tb strains studied. Overall, the LM and ManLAM levels did not differ between drug resistance categories, but ManLAM surface exposure increased with drug resistance. Infection of human macrophages revealed that DR-M.tb strains have decreased association compared to drug susceptible (DS) strains, and that the pre-XDR M.tb strain with the largest PDIMs:PIMs ratio had decreased uptake, but increased intracellular growth at early during infection compared to the DS-M.tb strain H37Rv. These findings suggest that PDIMs may play an important role in drug resistance and that an increase in hydrophobic cell envelope lipids may influence M.tb-host interactions.
Insights
Drug-resistant tuberculosis strains show altered cell envelope lipids, with increased phthiocerol dimycocerosates (PDIMs) relative to phosphatidyl-myo-inositol mannosides (PIMs). This lipid shift may influence Mycobacterium tuberculosis-host interactions and drug resistance.
Area of Science:
- Microbiology
- Biochemistry
- Immunology
Background:
- Drug-resistant (DR) Mycobacterium tuberculosis (M.tb) strains pose a significant public health threat.
- The M.tb cell envelope is crucial for its survival but its lipid composition in relation to drug resistance is not well understood.
Purpose of the Study:
- To investigate changes in peripheral cell envelope lipid levels in DR M.tb strains compared to drug-susceptible (DS) strains.
- To explore the functional implications of these lipid alterations on M.tb-host interactions.
Main Methods:
- Quantification of cell envelope lipids including phthiocerol dimycocerosates (PDIMs), phosphatidyl-myo-inositol mannosides (PIMs), lipomannan (LM), and mannose-capped lipoarabinomannan (ManLAM) in 22 M.tb strains with varying drug resistance profiles.
- Analysis of ManLAM surface exposure.
- Infection of human macrophages with DR and DS M.tb strains to assess bacterial association, uptake, and intracellular growth.
Main Results:
- A higher ratio of PDIMs to PIMs was observed in DR M.tb strains, with unique PDIM isomers detected.
- While overall LM and ManLAM levels were similar, ManLAM surface exposure increased with drug resistance.
- DR M.tb strains showed reduced association with macrophages, and a pre-extensively drug-resistant (pre-XDR) strain exhibited decreased uptake but increased early intracellular growth.
Conclusions:
- The PDIMs:PIMs ratio is a potential marker for M.tb drug resistance.
- Increased hydrophobic cell envelope lipids, particularly PDIMs, may contribute to M.tb drug resistance and modulate host-pathogen interactions.
More Related Videos
09:34An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis
Published on: August 16, 2021
10:43Polarization of M1 and M2 Human Monocyte-Derived Cells and Analysis with Flow Cytometry upon Mycobacterium tuberculosis Infection
Published on: September 18, 2020
Related Concept Videos
01:31Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
01:28Pulmonary Tuberculosis II
Here is a detailed explanation of its pathophysiology:
Transmission: The process begins when a person inhales droplet nuclei containing M. tuberculosis. These are typically released into the air when an individual with pulmonary or...
01:29Pulmonary Tuberculosis I
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
01:28Pulmonary Tuberculosis V
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the...
01:26Pulmonary Tuberculosis IV
Several diagnostic approaches are used to detect TB. The conventional method is the Tuberculin Skin Test (TST), also known as the Mantoux test. However, this method has...